This proposal is a continuation of a program project that, over the course of the last sixteen years, has dealt with problems in fundamental and applied neuroendocrinology as they apply to the fields of diabetes, pituitary and brain function and the biology of cell proliferation. The long-term objectives are to understand the role played by key proteins in the onset and progression of diabetes and its complications. It is proposed (1) to establish how angiogenic factors are regulated and identify the mechanisms which promote and/or limit their bioavailability; (2) to determine how dysfunction of these regulatory elements in disorders such as diabetes might mediate microvascular complications; (3) to characterize novel growth inhibitors and use these molecules to study diseases of cell proliferation; (4) to study the molecular biology of fibroblast growth factor; (5) its receptor; and (6) the regulation of their expression. These specific aims are to be supported by the presence of state-of-the-art cores of immunotechniques, nucleotide synthesis, peptide synthesis and sequencing, which serve on one hand as the backbone uniting a comprehensive research program in diabetes, pituitary, and growth factor biology and on the other as the necessary resource to develop and import novel and/or improved techniques and technology to the research projects to ensure that the program remains at the forefront of science.